Most periodontal diseases are considered to be a kind of infectious disease caused by indigenous microbes residing in the periodontal area. It has been revealed that a gram-negative anaerobic bacterium called Porphyromonas gingivalis (hereinafter abbreviated as “P. gingivalis”) is the most important pathogenic bacterium in the infections that cause adult periodontitis and rapidly progressive periodontitis (J. Clin. Periodontol., 15, 85-93, 1988, ibid 316-323, 1988; J. Dent. Res., 63, 441-451, 1984). In recent years, it has become known that proteases produced by P. gingivalis decompose periodontal tissue components such as collagen, and blood serum proteins involved in the body's natural defense system and are intimately related to the pathogenicity of P. gingivalis (Greiner D.: Biology of the Species Porphyromonas Gingivalis, Edited by Shah H. N., Mayrrand D. and Genco R. J., pp.227-243, CRC Press, Boca Raton, Ann Arbor, London, Tokyo, 1993). For example, Lys-gingipain (hereinafter sometimes abbreviated as “KGP”), a proteolytic enzyme having trypsin-like protease activity and produced by P. gingivalis, is known to have a high ability to digest high molecular weight kininogen and fibrinogen and considered to play a role in the onset of periodontal disease and destruction of periodontal tissues (J. Biol. Chem., 269, 406-411, 1994).
In order to prevent and treat periodontal disease, drugs for inhibiting the growth of bacteria are conventionally used. Useful drugs include, for example, antibiotics such as tetracycline and minocycline; natural products such as chamomile tincture and rhatany tincture; cyclohexadine, tranexamic acid and the like. However, these drugs have safety problems or other various problems such as unpleasant smell. Japanese Unexamined Patent Publication No. 97708/1993 discloses a periodontal therapeutic agent comprising an ATPase inhibitor, a cysteine protease inhibitor or the like as an active ingredient. However, the anti-periodontal disease effect of this therapeutic agent is unsatisfactory.
Japanese Patent No. 2529825 describes various peptidase substrate analogues but nowhere mentions peptide derivatives having a glutamic acid-lysine derivative structure as the basic skeleton, like the compound of the present invention. In addition, there is no description about compounds having KGP-specific inhibitory effects or compounds useful for treating periodontal diseases.